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Author

Christopher J. Hardy

Other affiliations: Johns Hopkins University
Bio: Christopher J. Hardy is an academic researcher from General Electric. The author has contributed to research in topics: Pulse sequence & Electromagnetic coil. The author has an hindex of 49, co-authored 193 publications receiving 8369 citations. Previous affiliations of Christopher J. Hardy include Johns Hopkins University.


Papers
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Journal ArticleDOI
TL;DR: The intrinsic and system SNR is applied to predict image SNR and has found satisfactory agreement with measurements on images, which indicates that the initial choice of pixel size is crucial in NMR.
Abstract: The fundamental limit for NMR imaging is set by an intrinsic signal-to-noise ratio (SNR) for a particular combination of rf antenna and imaging subjects. The intrinsic SNR is the signal from a small volume of material in the sample competing with electrical noise from thermally generated, random noise currents in the sample. The intrinsic SNR has been measured for a number of antenna-body section combinations at several different values of the static magnetic field and is proportional to B0. We have applied the intrinsic and system SNR to predict image SNR and have found satisfactory agreement with measurements on images. The relationship between SNR and pixel size is quite different in NMR than it is with imaging modalities using ionizing radiation, and indicates that the initial choice of pixel size is crucial in NMR. The analog of "contrast-detail-dose" plots for ionizing radiation imaging modalities is the "contrast-detail-time" plot in NMR, which should prove useful in choosing a suitable pixel array to visualize a particular anatomical detail for a given NMR receiving antenna.

760 citations

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TL;DR: Data scatter is recognized as the major factor inhibiting the diagnostic utility of quantitative NMR relaxation measurements, and only liver hepatoma can be reliably distinguished from normal liver based on a single T1 measurement.
Abstract: The longitudinal (T1) and transverse (T2) proton (1H) nuclear magnetic resonance (NMR) relaxation times of pathological human and animal tissues in the frequency range 1-100 MHz are archived, reviewed, and analyzed as a function of tissue of origin, NMR frequency, temperature, species, and in vivo versus in vitro status. T1 data from specific disease states of the bone, brain, breast, kidney, liver, muscle, pancreas, and spleen can be characterized by simple dispersions of the form T1 = AvB in the range 1-100 MHz with A and B empirically determined pathology-dependent constants. Pathological tissue T2 values are essentially independent of NMR frequency. Raw relaxation data, best-fit T1 parameters A and B, and the mean T2 values, are tabulated along with standard deviations and sample size to establish the normal range of pathological tissue relaxation times applicable to NMR imaging or in vitro NMR examination. Statistical analysis of relaxation data, assumed independent, reveals that most tumor and edematous tissue T1 values and some breast, liver, and muscle tumor T2 values are significantly elevated (p greater than or equal to 0.95) relative to normal, but do not differ significantly from other tumors and pathologies. Statistically significant abnormalities in the T1 values of some brain, breast, and lung tumors, and most pathological tissue T2 values could not, however, be demonstrated in the presence of large statistical errors. Both T1 and T2 in uninvolved tissue from tumor-bearing animals or organs do not demonstrate statistically significant differences from normal when considered as a group, suggesting no appreciable systemic effects associated with the presence of tumors compared to the statistical uncertainty. Statistical prediction analysis for both T1 and T2 indicates that of all the tissues studied, only liver hepatoma can be reliably distinguished from normal liver based on a single T1 measurement (p greater than or equal to 0.95) given the scatter in the current published data. Indeed, data scatter, not easily attributable to temperature, species, in vivo versus in vitro status, the inclusion of implanted or chemical induced tumors, or the possible existence of multiple component relaxation, is recognized as the major factor inhibiting the diagnostic utility of quantitative NMR relaxation measurements. Malignancy indexes that combine T1 and T2 data as a diagnostic indicator suffer similar problems of uncertainty. The literature review reveals a dearth of information on the temperature and frequency dependence of pathological tissue relaxation and the possible existence of multiple relaxation components.(ABSTRACT TRUNCATED AT 400 WORDS)

480 citations

Journal ArticleDOI
TL;DR: In this article, a superconducting magnetic resonance (MR) imager that provides direct access to the patient and permits interactive MR-guided interventional procedures was designed and constructed, and images were obtained in several anatomic regions with use of routine pulse sequences.
Abstract: PURPOSE: To develop a superconducting magnetic resonance (MR) imager that provides direct access to the patient and permits interactive MR-guided interventional procedures. MATERIALS AND METHODS: A 0.5-T superconducting magnet that allows a region of vertical access to the patient was designed and constructed. This magnet was integrated with newly designed shielded gradient coils, flexible surface coils, and nonmagnetic displays and with position-monitoring probes and device-tracking instrumentation. RESULTS: The magnet homogeneity was 12.3 ppm, and the gradient field was linear to within 1% over an imaging region 30 cm in diameter. The signal-to-noise ratio was 10% higher than in a comparable 0.5-T superconducting imager. Images were obtained in several anatomic regions with use of routine pulse sequences. Interactive image plane selection and near real-time imaging, with use of fast gradient-recalled echo sequences, were demonstrated at a rate of one image every 1.5 seconds. CONCLUSION: MR-guided interv...

423 citations

Journal ArticleDOI
TL;DR: The decrease in the ratio of phosphocreatine to ATP during hand-grip exercise in patients with myocardial ischemia reflects a transient imbalance between oxygen supply and demand in myocardium with compromised blood flow.
Abstract: Background. The maintenance of cellular levels of high-energy phosphates is required for myocardial function and preservation. In animals, severe myocardial ischemia is characterized by the rapid loss of phosphocreatine and a decrease in the ratio of phosphocreatine to ATP. Methods. To determine whether ischemic metabolic changes are detectable in humans, we recorded spatially localized phosphorus-31 nuclear-magnetic-resonance (31P NMR) spectra from the anterior myocardium before, during, and after isometric hand-grip exercise. Results. The mean (±SD) ratio of phosphocreatine to ATP in the left ventricular wall when subjects were at rest was 1.72±0.15 in normal subjects (n = 11) and 1.59±0.31 in patients with nonischemic heart disease (n = 9), and the ratio did not change during hand-grip exercise in either group. However, in patients with coronary heart disease and ischemia due to severe stenosis (≥70 percent) of the left anterior descending or left main coronary arteries (n = 16), the ratio dec...

337 citations

Journal ArticleDOI
TL;DR: A prototype system is constructed to assess MRI thermal monitoring and the localization of the heat zone in muscle and acquisitions are optimized for high temperature sensitive images that yield the thermal diffusivity, heat flow time constant and the focal spot size in muscle.
Abstract: Deep lying soft tissue tumors may be treated by a nonincisional surgical procedure executed inside an MR imaging system using a thermal effect delivered by a focused ultrasound transducer. A prototype system is constructed to assess MRI thermal monitoring and the localization of the heat zone in muscle. The temperature distribution of the focal spot is imaged with MRI while mechanically moving the transducer with an hydraulic 3-axis positioner. Acoustic power is applied with a spherical shell transducer using 1- to 10-s duration pulses at frequencies of 1.5 MHz to selectively coagulate tissue at 60-70 degrees C. The procedure is monitored with a series of fast second gradient echo, T1-weighted, temperature sensitive MR sequences. Acquisitions are optimized for high temperature sensitive images that yield the thermal diffusivity, heat flow time constant and the focal spot size in muscle. MR temperature maps of muscle provide localization and dosimetry both in the focal region and near field.

282 citations


Cited by
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TL;DR: A novel approach to correcting for intensity nonuniformity in magnetic resonance (MR) data is described that achieves high performance without requiring a model of the tissue classes present, and is applied at an early stage in an automated data analysis, before a tissue model is available.
Abstract: A novel approach to correcting for intensity nonuniformity in magnetic resonance (MR) data is described that achieves high performance without requiring a model of the tissue classes present. The method has the advantage that it can be applied at an early stage in an automated data analysis, before a tissue model is available. Described as nonparametric nonuniform intensity normalization (N3), the method is independent of pulse sequence and insensitive to pathological data that might otherwise violate model assumptions. To eliminate the dependence of the field estimate on anatomy, an iterative approach is employed to estimate both the multiplicative bias field and the distribution of the true tissue intensities. The performance of this method is evaluated using both real and simulated MR data.

4,613 citations

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TL;DR: The present review aims to provide a reassessment of the factors important for folding in light of current knowledge, including contributions to the free energy of folding arising from electrostatics, hydrogen-bonding and van der Waals interactions, intrinsic propensities, and hydrophobic interactions.
Abstract: T e purpose of this review is to assess the nature and magnitudes of the dominant forces in protein folding. Since proteins are only marginally stable at room temperature,’ no type of molecular interaction is unimportant, and even small interactions can contribute significantly (positively or negatively) to stability (Alber, 1989a,b; Matthews, 1987a,b). However, the present review aims to identify only the largest forces that lead to the structural features of globular proteins: their extraordinary compactness, their core of nonpolar residues, and their considerable amounts of internal architecture. This review explores contributions to the free energy of folding arising from electrostatics (classical charge repulsions and ion pairing), hydrogen-bonding and van der Waals interactions, intrinsic propensities, and hydrophobic interactions. An earlier review by Kauzmann (1959) introduced the importance of hydrophobic interactions. His insights were particularly remarkable considering that he did not have the benefit of known protein structures, model studies, high-resolution calorimetry, mutational methods, or force-field or statistical mechanical results. The present review aims to provide a reassessment of the factors important for folding in light of current knowledge. Also considered here are the opposing forces, conformational entropy and electrostatics. The process of protein folding has been known for about 60 years. In 1902, Emil Fischer and Franz Hofmeister independently concluded that proteins were chains of covalently linked amino acids (Haschemeyer & Haschemeyer, 1973) but deeper understanding of protein structure and conformational change was hindered because of the difficulty in finding conditions for solubilization. Chick and Martin (191 1) were the first to discover the process of denaturation and to distinguish it from the process of aggregation. By 1925, the denaturation process was considered to be either hydrolysis of the peptide bond (Wu & Wu, 1925; Anson & Mirsky, 1925) or dehydration of the protein (Robertson, 1918). The view that protein denaturation was an unfolding process was

3,570 citations

Journal ArticleDOI
TL;DR: The image intensity in magnetic resonance magnitude images in the presence of noise is shown to be governed by a Rician distribution and low signal intensities (SNR < 2) are therefore biased due to the noise.
Abstract: The image intensity in magnetic resonance magnitude images in the presence of noise is shown to be governed by a Rician distribution. Low signal intensities (SNR < 2) are therefore biased due to the noise. It is shown how the underlying noise can be estimated from the images and a simple correction scheme is provided to reduce the bias. The noise characteristics in phase images are also studied and shown to be very different from those of the magnitude images. Common to both, however, is that the noise distributions are nearly Gaussian for SNR larger than two.

2,425 citations

Journal ArticleDOI
TL;DR: Methods for simultaneously acquiring and subsequently combining data from a multitude of closely positioned NMR receiving coils are described, conceptually similar to phased array radar and ultrasound and hence the techniques are called the “NMR phased array.”
Abstract: We describe methods for simultaneously acquiring and subsequently combining data from a multitude of closely positioned NMR receiving coils. The approach is conceptually similar to phased array radar and ultrasound and hence we call our techniques the “NMR phased array.” The NMR phased array offers the signal-to-noise ratio (SNR) and resolution of a small surface coil over fields-of-view (FOV) normally associated with body imaging with no increase in imaging time. The NMR phased array can be applied to both imaging and spectroscopy for all pulse sequences. The problematic interactions among nearby surface coils is eliminated (a) by overlapping adjacent coils to give zero mutual inductance, hence zero interaction, and (b) by attaching low input impedance preamplifiers to all coils, thus eliminating interference among next nearest and more distant neighbors. We derive an algorithm for combining the data from the phased array elements to yield an image with optimum SNR. Other techniques which are easier to implement at the cost of lower SNR are explored. Phased array imaging is demonstrated with high resolution (512 × 512, 48-cm FOV, and 32-cm FOV) spin-echo images of the thoracic and lumbar spine. Data were acquired from four-element linear spine arrays, the first made of 12-cm square coils and the second made of 8-cm square coils. When compared with images from a single 15 × 30-cm rectangular coil and identical imaging parameters, the phased array yields a 2X and 3X higher SNR at the depth of the spine ( ∼ 7 cm). © 1990 Academic Press, Inc.

2,360 citations

Journal ArticleDOI
TL;DR: A comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism is presented, encompassing the pathways and regulation of Cr biosynthesis and degradation, species and tissue distribution of the enzymes and metabolites involved, and of the inherent implications for physiology and human pathology.
Abstract: The goal of this review is to present a comprehensive survey of the many intriguing facets of creatine (Cr) and creatinine metabolism, encompassing the pathways and regulation of Cr biosynthesis an...

2,332 citations